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"Heparin" Action Enhancement of the action of the serine protease inhibitors AT III and heparin co factor II.

the binding of heparin to AT III and an exponential increase in its antifactor Xa activity, a further 13 sugars are needed to cross link the AT III and thrombin in order to increase ATIII's antithrombin action Heparin does not inhibit thrombin bound to fibrin or Xa bound to platelets. Unfractioned heparin has a Xa:Thrombin inhibiting effect of 1:1. The low molecular weight heparins have varying Xa:Thrombin inhibiting effects Protamine sulphate - has intrinsic anticoagulation properties of its own and must be titrated. 1.3mg/Kg/100 units unfractionated heparin Adverse effects Hypotension The Heparin/Protamine complex releases histamine, predominantly from lung macrophages. Pulmonary hypertension - Heparin/Protamine complex activates complement and causes thromboxane release. Pre-treatment with a cyclooxygenase inhibitor is said to help

Allergic reactions True mediated by antibodies formed on prior exposure to protamine Previous bypass surgery Protamine containing insulins Fish allergy ??? vasectomised males Immediate mediated by complement UFH 30% SC dose absorbed Highly protein bound LMWH 80% due to less binding to endothelium less Less renal clearence

Biokinetics AbsorptionDistribution excretion

APTT Prolonged = A decrease to less than 30% activity of all the coagulation factors Heparin therapy Haemophilia Massive blood transfusions High dose coumarin anticoagulation

Action Blockage of vitamin K reductase and vitamin K epoxide reductase:

Warfarin

The inhibition of the gamma carboxylase leads to an accumulation of the inactive precursors of the clotting factors - also known as protein induced by vitamin K absence - PIVKA. This affects factors II, VII, IX, X, Protein C, Protein S - the serine protease enzymes

INR Prolonged = Deficiency of factor I, II, V, VII or X. Coumarin anticoagulation therapy Vitamin K deficiency Severe Liver disease Massive blood transfusions Disseminated intravascular coagulation High dose heparin therapy Antithrombin III activity assay Decreased by consumption Sepsis Disseminated intravascular coagulation Deep vein thrombosis or pulmonary embolism Decreased due to low levels of the molecule Decreased synthesis of a normal AT III molecule - Autosomal dominant Production of a dysfunctional AT III molecule - Autosomal dominant Lupus Anticoagulant Majority of patients do not have systemic lupus erythematosus nor any tendency towards increased bleeding IgG directed against the Xa-V-Phospholipid complex Markedly prolonges the aPTT Clinical tendency towards excessive thrombosis Occurs in a variety of conditions Essentially normal patients

Lupus 5-10% of patients Infectious diseases Rheumatoid arthritis Lymphoma Prostatic cancer Acquired immunde deficiency syndrome Drug exposure - chlorpromazine, procainamide and antibiotics

Laboratory tests to isolate the lupus anticoagulant Cardiolipin adsorption Reptilase Test Dilute aPTT Kaolin clotting time Platelet neutralisation procedure.

Thrombin is added to plasma and the time taken to form a clot is recorded Normal is less than 15 seconds Prolonged due to inhibition of thrombin Heparin Fibrin degradation products Lupus anticoagulant Prolonged due to abnormal fibrinogen ACT Prolonged times may be due to Heparin effect Hypothermia Platelet dysfunction Haemodilution Cardioplegic solutions Hypofibrinogenaemia Factor deficiencies

High Risk of Pre-operative Thrombosis Venous thrombosis An acute episode of Deep vein thrombosis within the last three months Multiple previous acute episodes of deep vein thrombosis Hereditary thrombophilic state Active carcinoma Atrial/arterial thrombosis

Clinical criteria Previous cerebrovascular accident Female over the age of 75 years Hypertensive patients Left ventricular dysfunction Congestive Cardiac Failure Trans-oesophageal criteria Complex aortic plaque Existing left atrial thrombus Dense spontaneous echocardiographic contrast

Mechanical Heart Valve Previous valvular thrombosis Caged-ball (Star-Edwards) and tilt (Bjork-Shiley) type valves in the mitral position
Bleeding Time 1/2/11 Data Interpretation Venkatesh A-Z standard incision made on forearm using a pricking device or a template. BP cuff inflated to 40mmHg. incision dabbed with filter paper every 30 seconds until bleeding time stops. normal value = 2-9 minutes. infrequently used c/o susceptible to much variation if prolonged -> platelet function problem: wWD aspirin heparin post cardiopulmonary bypass uraemia post-haemodialysis beta-lactam antibiotic use NSAIDS

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